Antiretroviral resistance in HIV: Difference between revisions

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* Genotyping sequences reverse transcriptase, integrase, and protease
 +
*Genotyping sequences reverse transcriptase, integrase, and protease
−
* Resistance point mutations names as wild-type amino acid, position, and mutant amino acid (e.g. K '''103''' N)
 +
*Resistance point mutations names as wild-type amino acid, position, and mutant amino acid (e.g. K '''103''' N)
−
* Bulk sequencing can only detect mutations that represent >20% of HIV
 +
*Bulk sequencing can only detect mutations that represent >20% of HIV
   
  +
==Common Mutations==
  +
  +
*NRTIs
  +
**'''M184V/I''' confers resistance to [[lamivudine]], [[emtricitabine]], and [[abacavir]], but increases susceptibility to [[tenofovir]], so combinations that include [[tenofovir]] are still safe to use
  +
**'''K65R''' confers resistance to [[lamivudine]], [[emtricitabine]], and [[abacavir]]
  +
**'''TAMS (M41L, D76N, K70R, L210W, T215Y, K219Q)''' confer resistance to basically all NRTIs as they increase in number
  +
**'''Q151M, 69SSS''' confers resistance to NRTIs
  +
*NNRTIs
  +
**'''K103N''' confers resistance to [[efavirenz]] and [[nevirapine]]
  +
**'''Y181C''' confers resistance to [[nevirapine]] and other NNRTIs
  +
**'''E138K and K101E''' confer resistance to [[rilpivirine]] and other NNRTIs
  +
**'''I50L''' confers resistance to [[atazanavir]]
  +
*INSTIs
  +
**'''N155H and Q148H/R?K''' confer resistance to [[raltegravir]] and [[elvitegravir]]
  +
**'''Y143C''' confers resistance to [[raltegravir]]
  +
**'''R263K''' confers resistance to [[dolutegravir]]
  +
  +
==All Mutations==
 
{| class="wikitable"
  
{| class="wikitable"
−
! Drug
 +
!Drug
−
! Mutation
 +
!Mutation
−
! Notes
 +
!Notes
 
|-
  
|-
−
! colspan=3 | NRTIs
 +
! colspan="3" |NRTIs
 
|-
  
|-
−
| rowspan=7 | 69 insertion complex multi-NRTI resistance
 +
| rowspan="7" |69 insertion complex
−
| M '''41''' '''L'''
 +
|M'''41L'''
  +
| rowspan="7" |multi-NRTI resistance
−
|
  
 
|-
  
|-
−
| A '''62''' '''V'''
 +
|A'''62V'''
−
|
  
 
|-
  
|-
−
| * '''69''' '''insert'''
 +
|* '''69''' '''insert'''
−
|
  
 
|-
  
|-
−
| K '''70''' '''R'''
 +
|K'''70R'''
−
|
  
 
|-
  
|-
−
| L '''210''' '''W'''
 +
|L'''210W'''
−
|
  
 
|-
  
|-
−
| T '''215''' '''Y F'''
 +
|T'''215YF'''
−
|
  
 
|-
  
|-
−
| K '''219''' '''Q E'''
 +
|K'''219QE'''
−
|
  
 
|-
  
|-
−
| rowspan=5 | 151 complex multi-NRTI resistance
 +
| rowspan="5" |151 complex
−
| A '''62''' '''V'''
 +
|A'''62V'''
  +
| rowspan="5" |multi-NRTI resistance
−
|
  
 
|-
  
|-
−
| V '''75''' '''I'''
 +
|V'''75I'''
−
|
  
 
|-
  
|-
−
| F '''77''' '''L'''
 +
|F'''77L'''
−
|
  
 
|-
  
|-
−
| F '''116''' '''Y'''
 +
|F'''116Y'''
−
|
  
 
|-
  
|-
−
| Q '''151''' '''M'''
 +
|Q'''151M'''
−
|
  
 
|-
  
|-
−
| rowspan=6 | Thymidine analogue-associated mutations (TAMs) multi-NRTI resistance
 +
| rowspan="6" |Thymidine analogue-associated mutations (TAMs)
−
| M '''41''' '''L'''
 +
|M'''41L'''
−
| rowspan=6 | resistance to AZT and d4T; resistance to others is proportional to the number of TAMs
 +
| rowspan="6" |resistance to AZT and d4T; resistance to others is proportional to the number of TAMs, and with 4 or more mutations there is resistance to essentially all NRTIs
 
|-
  
|-
−
| D '''67''' '''N'''
 +
|D'''67N'''
 
|-
  
|-
−
| K '''70''' '''R'''
 +
|K'''70R'''
 
|-
  
|-
−
| L '''210''' '''W'''
 +
|L'''210W'''
 
|-
  
|-
−
| T '''215''' '''Y F'''
 +
|T'''215Y/F'''
 
|-
  
|-
−
| K '''219''' '''Q W'''
 +
|K'''219Q/W'''
 
|-
  
|-
−
| rowspan=4 | [[Abacavir]]
 +
| rowspan="4" |[[Abacavir]]
−
| K '''65''' '''R E N'''
 +
|K'''65R/E/N'''
  +
|common
−
|
  
 
|-
  
|-
−
| L '''74''' '''V'''
 +
|L'''74V'''
 
|
  
|
 
|-
  
|-
−
| Y '''115''' '''F'''
 +
|Y'''115F'''
 
|
  
|
 
|-
  
|-
−
| M '''184''' '''V'''
 +
|M'''184V'''
−
| common; can still use TDF, AZT
 +
|common; can still use TDF, AZT
 
|-
  
|-
−
| rowspan=2 | [[Emtricitabine]]
 +
| rowspan="2" |[[Emtricitabine]]
−
| K '''65''' '''R E N'''
 +
|K'''65R/E/N'''
  +
|common
−
|
  
 
|-
  
|-
−
| M '''184''' '''V I'''
 +
|M'''184V/I'''
−
| common; can use ABC (if M184I), TDF, AZT
 +
|common; can use ABC (if M184I), TDF, AZT; can still use FTC in combination with TDF or TAF
 
|-
  
|-
−
| rowspan=2 | [[Lamivudine]]
 +
| rowspan="2" |[[Lamivudine]]
−
| K '''65 '''R E N'''
 +
|K'''65'''R/E/N
  +
|common
−
|
  
 
|-
  
|-
−
| M '''184''' '''V I'''
 +
|M'''184V/I'''
−
| common; can use ABC (if M184I), TDF, AZT
 +
|common; can use ABC (if M184I), TDF, AZT; can still use 3TC in combination with TDF or TAF
 
|-
  
|-
−
| rowspan=2 | [[Tenofovir]]
 +
| rowspan="2" |[[Tenofovir]]
−
| K '''65''' '''R E N'''
 +
|K'''65R/E/N'''
  +
|common
−
|
  
 
|-
  
|-
−
| K '''70''' '''E'''
 +
|K'''70E'''
 
|
  
|
 
|-
  
|-
−
| rowspan=6 | [[Zidovudine]]
 +
| rowspan="6" |[[Zidovudine]]
−
| M '''41''' '''L'''
 +
|M'''41L'''
 
|
  
|
 
|-
  
|-
−
| D '''67''' '''N'''
 +
|D'''67N'''
 
|
  
|
 
|-
  
|-
−
| K '''70''' '''R'''
 +
|K'''70R'''
 
|
  
|
 
|-
  
|-
−
| L '''210''' '''W'''
 +
|L'''210W'''
 
|
  
|
 
|-
  
|-
−
| T '''215''' '''Y F'''
 +
|T'''215Y/F'''
 
|
  
|
 
|-
  
|-
−
| K '''219''' '''Q E'''
 +
|K'''219Q/E'''
 
|
  
|
 
|-
  
|-
−
! colspan=3 | NNRTIs
 +
! colspan="3" |NNRTIs
 
|-
  
|-
−
| rowspan=7 | [[Doravirine]]
 +
| rowspan="7" |[[Doravirine]]
−
| V '''106''' '''A''' I '''M''' T
 +
|V'''106A'''/I/'''M'''/T
 
|
  
|
 
|-
  
|-
−
| Y '''188''' C '''L''' H
 +
|Y'''188'''C/'''L'''/H
 
|
  
|
 
|-
  
|-
−
| G '''190''' E
 +
|G'''190'''E
 
|
  
|
 
|-
  
|-
−
| P '''225''' H
 +
|P'''225'''H
 
|
  
|
 
|-
  
|-
−
| F '''227''' C L R
 +
|F'''227'''C/L/R
 
|
  
|
 
|-
  
|-
−
| M '''230''' L
 +
|M'''230'''L
 
|
  
|
 
|-
  
|-
−
| L '''234''' I
 +
|L'''234'''I
 
|
  
|
 
|-
  
|-
−
| rowspan=10 | [[Efavirenz]]
 +
| rowspan="10" |[[Efavirenz]]
−
| L '''100''' '''I'''
 +
|L'''100I'''
 
|
  
|
 
|-
  
|-
−
| K '''101''' '''P'''
 +
|K'''101P'''
 
|
  
|
 
|-
  
|-
−
| K '''103''' '''N S'''
 +
|K'''103N'''/'''S'''
 
|
  
|
 
|-
  
|-
−
| V '''106''' '''M'''
 +
|V'''106M'''
 
|
  
|
 
|-
  
|-
−
| V '''108''' '''I'''
 +
|V'''108I'''
 
|
  
|
 
|-
  
|-
−
| Y '''181''' '''C I'''
 +
|Y'''181C'''/'''I'''
 
|
  
|
 
|-
  
|-
−
| Y '''188''' '''L'''
 +
|Y'''188L'''
 
|
  
|
 
|-
  
|-
−
| G '''190''' '''S A'''
 +
|G'''190S'''/'''A'''
 
|
  
|
 
|-
  
|-
−
| P '''225''' '''H'''
 +
|P'''225H'''
 
|
  
|
 
|-
  
|-
−
| M '''230''' '''L'''
 +
|M'''230L'''
 
|
  
|
 
|-
  
|-
−
| rowspan=9 | [[Nevirapine]]
 +
| rowspan="9" |[[Nevirapine]]
−
| L '''100''' '''I'''
 +
|L'''100I'''
 
|
  
|
 
|-
  
|-
−
| K '''101''' '''P'''
 +
|K'''101P'''
 
|
  
|
 
|-
  
|-
−
| K '''103''' '''N S'''
 +
|K'''103N'''/'''S'''
 
|
  
|
 
|-
  
|-
−
| V '''106''' '''A M'''
 +
|V'''106A'''/'''M'''
 
|
  
|
 
|-
  
|-
−
| V '''108''' '''I'''
 +
|V'''108I'''
 
|
  
|
 
|-
  
|-
−
| Y '''181''' '''C I'''
 +
|Y'''181C'''/'''I'''
  +
|common
−
|
  
 
|-
  
|-
−
| Y '''188''' '''C L H'''
 +
|Y'''188C'''/'''L'''/'''H'''
 
|
  
|
 
|-
  
|-
−
| G '''190''' '''A'''
 +
|G'''190A'''
 
|
  
|
 
|-
  
|-
−
| M '''230''' '''L'''
 +
|M'''230L'''
 
|
  
|
 
|-
  
|-
−
| rowspan=9 | [[Rilpivirine]]
 +
| rowspan="9" |[[Rilpivirine]]
−
| L '''100''' '''I'''
 +
|L'''100I'''
 
|
  
|
 
|-
  
|-
−
| K '''101''' '''E P'''
 +
|K'''101E'''/'''P'''
  +
|common
−
|
  
 
|-
  
|-
−
| E '''138''' '''A G K Q R'''
 +
|E'''138A'''/'''G'''/'''K'''/'''Q'''/'''R'''
  +
|common
−
|
  
 
|-
  
|-
−
| V '''179''' '''L'''
 +
|V'''179L'''
 
|
  
|
 
|-
  
|-
−
| Y '''181''' '''C I V'''
 +
|Y'''181C'''/'''I'''/'''V'''
  +
|common
−
|
  
 
|-
  
|-
−
| Y '''188''' '''L'''
 +
|Y'''188L'''
 
|
  
|
 
|-
  
|-
−
| H '''221''' '''Y'''
 +
|H'''221Y'''
 
|
  
|
 
|-
  
|-
−
| F '''227''' '''C'''
 +
|F'''227C'''
 
|
  
|
 
|-
  
|-
−
| M '''230''' '''I L'''
 +
|M'''230I'''/'''L'''
 
|
  
|
 
|-
  
|-
−
! colspan=3 | Protease inhibitors
 +
! colspan="3" |Protease inhibitors
 
|-
  
|-
−
| rowspan=24 | [[Atazanavir]]
 +
| rowspan="24" |[[Atazanavir]]
−
| L '''10''' I F V C
 +
|L'''10'''I/F/V/C
 
|
  
|
 
|-
  
|-
−
| G '''16''' E
 +
|G'''16'''E
 
|
  
|
 
|-
  
|-
−
| K '''20''' R M I T V
 +
|K'''20'''R/M/I/T/V
 
|
  
|
 
|-
  
|-
−
| L '''24''' I
 +
|L'''24'''I
 
|
  
|
 
|-
  
|-
−
| V '''32''' I
 +
|V'''32'''I
 
|
  
|
 
|-
  
|-
−
| L '''33''' I F V
 +
|L'''33'''I/F/V
 
|
  
|
 
|-
  
|-
−
| E '''34''' Q
 +
|E'''34'''Q
 
|
  
|
 
|-
  
|-
−
| M '''36''' I L V
 +
|M'''36'''I/L/V
 
|
  
|
 
|-
  
|-
−
| M '''46''' I L
 +
|M'''46'''I/L
 
|
  
|
 
|-
  
|-
−
| G '''48''' V
 +
|G'''48'''V
 
|
  
|
 
|-
  
|-
−
| I '''50''' '''L'''
 +
|I'''50L'''
  +
|common
−
|
  
 
|-
  
|-
−
| F '''53''' L Y
 +
|F'''53'''L/Y
 
|
  
|
 
|-
  
|-
−
| I '''54''' L V M T A
 +
|I'''54'''L/V/M/T/A
 
|
  
|
 
|-
  
|-
−
| D '''60''' E
 +
|D'''60'''E
 
|
  
|
 
|-
  
|-
−
| I '''62''' V
 +
|I'''62'''V
 
|
  
|
 
|-
  
|-
−
| I '''64''' L M V
 +
|I'''64'''L/M/V
 
|
  
|
 
|-
  
|-
−
| A '''71''' V I T L
 +
|A'''71'''V/I/T/L
 
|
  
|
 
|-
  
|-
−
| G '''73''' C S T A
 +
|G'''73'''C/S/T/A
 
|
  
|
 
|-
  
|-
−
| V 82 A T F I
 +
|V82A/T/F/I
 
|
  
|
 
|-
  
|-
−
| I '''84''' '''V'''
 +
|I'''84V'''
 
|
  
|
 
|-
  
|-
  +
|I85V
−
| I 85 V
  
 
|
  
|
 
|-
  
|-
−
| N '''88''' '''S'''
 +
|N'''88S'''
 
|
  
|
 
|-
  
|-
  +
|L90M
−
| L 90 M
  
 
|
  
|
 
|-
  
|-
  +
|I93L/M
−
| I 93 L M
  
 
|
  
|
 
|-
  
|-
−
| rowspan=10 | [[Darunavir]]
 +
| rowspan="10" |[[Darunavir]]
  +
|V11I
−
| V 11 I
  
 
|
  
|
 
|-
  
|-
  +
|V32I
−
| V 32 I
  
 
|
  
|
 
|-
  
|-
  +
|L33F
−
| L 33 F
  
 
|
  
|
 
|-
  
|-
−
| I '''47''' '''V'''
 +
|I'''47V'''
 
|
  
|
 
|-
  
|-
−
| I '''50''' '''V'''
 +
|I'''50V'''
 
|
  
|
 
|-
  
|-
−
| I '''54''' '''M L'''
 +
|I'''54M'''/'''L'''
 
|
  
|
 
|-
  
|-
  +
|T74P
−
| T 74 P
  
 
|
  
|
 
|-
  
|-
−
| L '''76''' '''V'''
 +
|L'''76V'''
 
|
  
|
 
|-
  
|-
−
| I '''84''' '''V'''
 +
|I'''84V'''
 
|
  
|
 
|-
  
|-
  +
|L89V
−
| L 89 V
  
 
|
  
|
 
|-
  
|-
−
! colspan=3 | INSTIs
 +
! colspan="3" |INSTIs
 
|-
  
|-
−
| rowspan=5 | [[Bictegravir]]
 +
| rowspan="5" |[[Bictegravir]]
  +
|G118R
−
| G 118 R
  
 
|
  
|
 
|-
  
|-
  +
|E138K
−
| E 138 K
  
 
|
  
|
 
|-
  
|-
  +
|G140S
−
| G 140 S
  
 
|
  
|
 
|-
  
|-
−
| Q '''148''' '''H'''
 +
|Q'''148H'''
 
|
  
|
 
|-
  
|-
−
| R '''263''' '''K'''
 +
|R'''263K'''
 
|
  
|
 
|-
  
|-
−
| rowspan=8 | [[Cabotegravir]]
 +
| rowspan="8" |[[Cabotegravir]]
  +
|T66K
−
| T 66 K
  
 
|
  
|
 
|-
  
|-
−
| G '''118''' '''R'''
 +
|G'''118R'''
 
|
  
|
 
|-
  
|-
−
| E 138 A K T
 +
|E138A/K/T
 
|
  
|
 
|-
  
|-
−
| G '''140''' A C '''R''' S
 +
|G'''140'''A/C/'''R'''/S
 
|
  
|
 
|-
  
|-
−
| Q '''148''' '''H K R'''
 +
|Q'''148H'''/'''K/R'''
 
|
  
|
 
|-
  
|-
  +
|S153F/Y
−
| S 153 F Y
  
 
|
  
|
 
|-
  
|-
  +
|N155H
−
| N 155 H
  
 
|
  
|
 
|-
  
|-
−
| R '''263''' '''K'''
 +
|R'''263K'''
 
|
  
|
 
|-
  
|-
−
| rowspan=7 | [[Dolutegravir]]
 +
| rowspan="7" |[[Dolutegravir]]
−
| G '''118''' '''R'''
 +
|G'''118R'''
 
|
  
|
 
|-
  
|-
  +
|F121Y
−
| F 121 Y
  
 
|
  
|
 
|-
  
|-
−
| E 138 A K T
 +
|E138A/K/T
 
|
  
|
 
|-
  
|-
  +
|G140A/S
−
| G 140 A S
  
 
|
  
|
 
|-
  
|-
−
| Q '''148''' '''H K R'''
 +
|Q'''148H'''/'''K'''/'''R'''
 
|
  
|
 
|-
  
|-
  +
|N155H
−
| N 155 H
  
 
|
  
|
 
|-
  
|-
−
| R '''263''' '''K'''
 +
|R'''263K'''
  +
|common
−
|
  
 
|-
  
|-
−
| rowspan=8 | [[Elvitegravir]]
 +
| rowspan="8" |[[Elvitegravir]]
−
| T '''66''' '''I''' A K
 +
|T'''66I'''/A/K
 
|
  
|
 
|-
  
|-
−
| E '''92''' '''Q''' G
 +
|E'''92Q'''/G
 
|
  
|
 
|-
  
|-
  +
|T97A
−
| T 97 A
  
 
|
  
|
 
|-
  
|-
−
| F '''121''' '''Y'''
 +
|F'''121Y'''
 
|
  
|
 
|-
  
|-
−
| S '''147''' '''G'''
 +
|S'''147G'''
 
|
  
|
 
|-
  
|-
−
| Q '''148''' '''H K R'''
 +
|Q'''148H'''/'''K'''/'''R'''
  +
|common
−
|
  
 
|-
  
|-
−
| N '''155''' '''H'''
 +
|N'''155H'''
  +
|common
−
|
  
 
|-
  
|-
−
| R '''263''' '''K'''
 +
|R'''263K'''
 
|
  
|
 
|-
  
|-
−
| rowspan=10 | [[Raltegravir]]
 +
| rowspan="10" |[[Raltegravir]]
  +
|L74M
−
| L 74 M
  
 
|
  
|
 
|-
  
|-
  +
|E92Q
−
| E 92 Q
  
 
|
  
|
 
|-
  
|-
  +
|T97A
−
| T 97 A
  
 
|
  
|
 
|-
  
|-
−
| F '''121''' '''Y'''
 +
|F'''121Y'''
 
|
  
|
 
|-
  
|-
  +
|E138A/K
−
| E 138 A K
  
 
|
  
|
 
|-
  
|-
  +
|G140A/S
−
| G 140 A S
  
 
|
  
|
 
|-
  
|-
−
| Y '''143''' '''R H C'''
 +
|Y'''143R'''/'''H'''/'''C'''
  +
|common
−
|
  
 
|-
  
|-
−
| Q '''148''' '''H K R'''
 +
|Q'''148H'''/'''K'''/'''R'''
  +
|common
−
|
  
 
|-
  
|-
−
| N '''155''' '''H'''
 +
|N'''155H'''
  +
|common
−
|
  
 
|-
  
|-
−
| R '''263''' '''K'''
 +
|R'''263K'''
 
|
  
|
 
|}
  
|}

Latest revision as of 08:59, 22 October 2020

  • Genotyping sequences reverse transcriptase, integrase, and protease
  • Resistance point mutations names as wild-type amino acid, position, and mutant amino acid (e.g. K 103 N)
  • Bulk sequencing can only detect mutations that represent >20% of HIV

Common Mutations

All Mutations

Drug Mutation Notes
NRTIs
69 insertion complex M41L multi-NRTI resistance
A62V
* 69 insert
K70R
L210W
T215YF
K219QE
151 complex A62V multi-NRTI resistance
V75I
F77L
F116Y
Q151M
Thymidine analogue-associated mutations (TAMs) M41L resistance to AZT and d4T; resistance to others is proportional to the number of TAMs, and with 4 or more mutations there is resistance to essentially all NRTIs
D67N
K70R
L210W
T215Y/F
K219Q/W
Abacavir K65R/E/N common
L74V
Y115F
M184V common; can still use TDF, AZT
Emtricitabine K65R/E/N common
M184V/I common; can use ABC (if M184I), TDF, AZT; can still use FTC in combination with TDF or TAF
Lamivudine K65R/E/N common
M184V/I common; can use ABC (if M184I), TDF, AZT; can still use 3TC in combination with TDF or TAF
Tenofovir K65R/E/N common
K70E
Zidovudine M41L
D67N
K70R
L210W
T215Y/F
K219Q/E
NNRTIs
Doravirine V106A/I/M/T
Y188C/L/H
G190E
P225H
F227C/L/R
M230L
L234I
Efavirenz L100I
K101P
K103N/S
V106M
V108I
Y181C/I
Y188L
G190S/A
P225H
M230L
Nevirapine L100I
K101P
K103N/S
V106A/M
V108I
Y181C/I common
Y188C/L/H
G190A
M230L
Rilpivirine L100I
K101E/P common
E138A/G/K/Q/R common
V179L
Y181C/I/V common
Y188L
H221Y
F227C
M230I/L
Protease inhibitors
Atazanavir L10I/F/V/C
G16E
K20R/M/I/T/V
L24I
V32I
L33I/F/V
E34Q
M36I/L/V
M46I/L
G48V
I50L common
F53L/Y
I54L/V/M/T/A
D60E
I62V
I64L/M/V
A71V/I/T/L
G73C/S/T/A
V82A/T/F/I
I84V
I85V
N88S
L90M
I93L/M
Darunavir V11I
V32I
L33F
I47V
I50V
I54M/L
T74P
L76V
I84V
L89V
INSTIs
Bictegravir G118R
E138K
G140S
Q148H
R263K
Cabotegravir T66K
G118R
E138A/K/T
G140A/C/R/S
Q148H/K/R
S153F/Y
N155H
R263K
Dolutegravir G118R
F121Y
E138A/K/T
G140A/S
Q148H/K/R
N155H
R263K common
Elvitegravir T66I/A/K
E92Q/G
T97A
F121Y
S147G
Q148H/K/R common
N155H common
R263K
Raltegravir L74M
E92Q
T97A
F121Y
E138A/K
G140A/S
Y143R/H/C common
Q148H/K/R common
N155H common
R263K
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